Neurology · 2025
Association of Platelet Aggregation With Markers of Alzheimer Disease Pathology in Middle-Aged Participants of the Framingham Heart Study.
СтатьяНазвание и аннотация: Перевод в очереди
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Ramos-Cejudo Jaime, Beiser Alexa S, Lu Sophia, Tanner Jeremy A, Scott Matthew R, He Tianshe, Ghosh Saptaparni, Johnson Keith A, Salinas Joel, Bubu Omonigho M, Fieremans Els, Convit Antonio, Pomara Nunzio, Wisniewski Thomas, Berger Jeffrey S, Osorio Ricardo S, Decarli Charles S, Johnson Andrew D, Seshadri Sudha
Аннотация
BACKGROUND AND OBJECTIVES: Vascular dysfunction contributes to Alzheimer disease (AD) and related dementias (ADRDs), but the underlying mechanisms remain unclear. Previous studies link midlife hemostasis and platelet aggregation measures to late-life dementia risk. We aimed to determine whether platelet aggregation in midlife is associated with imaging markers of AD pathology.
METHODS: In a cross-sectional study, we evaluated associations between platelet aggregation, measured by light transmission aggregometry, and amyloid (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET uptake in dementia-free, middle-aged adults from the Framingham Heart Study. Co-primary outcomes included amyloid and tau uptake in AD-vulnerable regions. We also examined an MRI-based cortical thickness signature of AD risk as a secondary outcome. We used multivariable regression models adjusted for demographic and clinical factors, considering potential nonlinear associations.
RESULTS: Platelet aggregation response was evaluated in 382 participants (mean age 56 ± 8 years, 53% female) approximately 1.2-1.5 years before amyloid and tau PET imaging. MRI data used for the AD signature were acquired together with PET imaging or within several months. The aggregation response exhibited a nonlinear association with AD pathology. Among those in the lowest tertile of adenosine diphosphate (ADP) response, platelet aggregation response was positively associated with increased amyloid in the precuneus (β = 0.047, p = 0.020) and tau in the rhinal (β = 0.077, p = 0.012), entorhinal (β = 0.066, p < 0.020), temporal global (β = 0.063, p = 0.031), and cortical (β = 0.064, p = 0.028) regions. For the secondary outcome analysis (n = 256), platelet aggregation response was negatively associated with the MRI-based cortical thickness signature of AD risk (β = -0.002, p < 0.035), consistent with a neurodegenerative pattern.
DISCUSSION: Our findings indicate that platelet aggregation is linked to PET and MRI markers of AD pathology as early as midlife. These findings support further investigation of platelet-mediated mechanisms in AD pathogenesis.
METHODS: In a cross-sectional study, we evaluated associations between platelet aggregation, measured by light transmission aggregometry, and amyloid (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET uptake in dementia-free, middle-aged adults from the Framingham Heart Study. Co-primary outcomes included amyloid and tau uptake in AD-vulnerable regions. We also examined an MRI-based cortical thickness signature of AD risk as a secondary outcome. We used multivariable regression models adjusted for demographic and clinical factors, considering potential nonlinear associations.
RESULTS: Platelet aggregation response was evaluated in 382 participants (mean age 56 ± 8 years, 53% female) approximately 1.2-1.5 years before amyloid and tau PET imaging. MRI data used for the AD signature were acquired together with PET imaging or within several months. The aggregation response exhibited a nonlinear association with AD pathology. Among those in the lowest tertile of adenosine diphosphate (ADP) response, platelet aggregation response was positively associated with increased amyloid in the precuneus (β = 0.047, p = 0.020) and tau in the rhinal (β = 0.077, p = 0.012), entorhinal (β = 0.066, p < 0.020), temporal global (β = 0.063, p = 0.031), and cortical (β = 0.064, p = 0.028) regions. For the secondary outcome analysis (n = 256), platelet aggregation response was negatively associated with the MRI-based cortical thickness signature of AD risk (β = -0.002, p < 0.035), consistent with a neurodegenerative pattern.
DISCUSSION: Our findings indicate that platelet aggregation is linked to PET and MRI markers of AD pathology as early as midlife. These findings support further investigation of platelet-mediated mechanisms in AD pathogenesis.